Dynamic Covalent Functionalization of DNA Origami via Iminoboronate Chemistry.

Reversible functionalization of DNA nanostructures is essential for their integration into dynamic biological constructs and biomedical applications. Current strategies typically rely on strand displacement or stimuli-responsive sequences, while approaches based on dynamic covalent chemistry remain largely unexplored. Yet, dynamic covalent bonds combine covalent stability with reversible exchange under mild conditions, offering adaptable and biologically compatible routes to modulate DNA nanostructures. Here, we report iminoboronate conjugation as a strategy for the reversible functionalization of DNA origami. Polyethylene glycol and cholesterol moieties bearing 2-formylphenylboronic acid are efficiently conjugated to DNA origami displaying α-effect amines, while conjugate displacement can be triggered by a small-molecule competitor. We further demonstrate the reversible anchoring of DNA origami to lipid bilayer systems, including both large and giant unilamellar vesicles. These findings establish iminoboronate chemistry as a robust, stimuli-responsive platform for interfacing DNA origami with functional moieties, paving the way for programmable nanodevices and adaptive biomimetic materials.